Hinokitiol induces DNA demethylation via DNMT1 and UHRF1 inhibition in colon cancer cells

BMC Cell Biology

Research Article

Young Ha Choi¹  Sun-Hwa Park¹  Hyeon Soo Kim¹  Jung Seon Seo¹  Ji Wook Moon² 

[1] Department of Anatomy, Institute of Human Genetics, Korea University College of Medicine, 73, Inchon-ro, Seongbuk-gu, 02841, Seoul, Republic of Korea;Department of Pathology, Korea University College of Medicine, 73, Inchon-ro, Seongbuk-gu, 02841, Seoul, Republic of Korea;

关键词: Hinokitiol;    DNA methylation;    Anti-tumor activities;    DNA methylation inhibitor;    Colonic neoplasm;   

DOI  :  10.1186/s12860-017-0130-3

 received in 2016-08-18, accepted in 2017-02-22,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundDNA hypermethylation is a key epigenetic mechanism for the silencing of many genes in cancer. Hinokitiol, a tropolone-related natural compound, is known to induce apoptosis and cell cycle arrest and has anti-inflammatory and anti-tumor activities. However, the relationship between hinokitiol and DNA methylation is not clear. The aim of our study was to explore whether hinokitiol has an inhibitory ability on the DNA methylation in colon cancer cells.ResultsMTT data showed that hinokitiol had higher sensitivity in colon cancer cells, HCT-116 and SW480, than in normal colon cells, CCD18Co. Hinokitiol reduced DNA methyltransferase 1 (DNMT1) and ubiquitin-like plant homeodomain and RING finger domain 1 (UHRF1) expression in HCT-116 cells. In addition, the expression of ten-eleven translocation protein 1 (TET1), a known DNA demethylation initiator, was increased by hinokitiol treatment. ELISA and FACS data showed that hinokitiol increased the 5-hydroxymethylcytosine (5hmC) level in the both colon cancer cells, but 5-methylcytosine (5mC) level was not changed. Furthermore, hinokitiol significantly restored mRNA expression of O6-methylguanine DNA methyltransferase (MGMT), carbohydrate sulfotransferase 10 (CHST10), and B-cell translocation gene 4 (BTG4) concomitant with reduction of methylation status in HCT-116 cells.ConclusionsThese results indicate that hinokitiol may exert DNA demethylation by inhibiting the expression of DNMT1 and UHRF1 in colon cancer cells.

【 授权许可】

CC BY   
© The Author(s). 2017